CXCR7 is involved in tumor development and metastasis in multiple malignancies. However, the functionand molecular mechanisms of action of CXCR7 in human cervical cancer are still unclear. In the present studya loss of-function approach was used to observe the effects of recombinant CXCR7 specific small interferingRNA pBSilence1.1 plasmids on biological behavior including proliferative activity and invasive potential, asindicated by MTT assays with the cervical cancer SiHa cell line in vitro. Reverse transcription polymerase chainreaction and Western blotting revealed that CXCR7 was downregulated in transfected compared with controlcells, associated with inhibited cell growth, invasiveness and migration. The expression of CXCR7 and CXCL12was also determined immunohistochemically in 152 paraffin-embedded, cervical squamous cell carcinoma(CSCC) and cervical intraepithelial neoplasia (CIN), or normal cervical epithelial to assess clinico-pathologicalpattern and CXCR7 status with respect to cell differentiation and lymph node metastasis in Uighur patients withCSCC. CXCR7 and CXCL12 expression was higher in cervical cancer than CIN and normal cervical mucosa,especially in those with higher stage and lymph node metastasis. CXCL12 appeared to be positively regulatedby CXCR7 at the post-transcriptional level in CSCC. We propose that aberrant expression of CXCR7 plays arole in carcinogenesis, differentiation and metastasis of CSCC, implying its use as a potential target for clinicalbiomarkers in differentiation and lymph node metastasis.